Exploration of the influence of small molecules on protein fibrillogenesis

Figure 1. The docking structures of hen egg-white lysozyme (HEWL, PDB ID: 2ZQ3) and the isomers of one of the tacrine-coumarin heterodimers (panel B) we studied.

Before I pursued my Ph.D. at CU Boulder, I spent around 1.5 years doing research as an undergrad researcher/research assistant in Dr. Steven Sheng-Shih Wang’s lab at National Taiwan University. The studies I conducted were mainly aimed to investigate the influence of small molecules on the amyloid fibrillogensis of hen egg-white lysozyme (HEWL), which shares high sequence homology to human lysozyme associated with hereditary non-neuropathic system amyloidosis. I examined the interplay between HEWL and a wide array of small molecules (brilliant blue G (BBG), brilliant blue R (BBR), erythrosine B (ErB), and a series of tacrine/acridone-coumarin heterodimers) with a variety of experimental techniques, including ThT binding assays, circular dichroism spectroscopy, ANS fluorescence spectroscopy, cytotoxicity assays, and transmission electron microscopic analysis, to name a few. In addition to experimental methods, I also employed molecular docking and molecular dynamics simulations to gain more insights into the interactions between the protein and small molecules. This is when my interest in computational methodlogies was sparkled. My efforts during this time also led to abundant research outputs, including 4 journal articles and 5 prizes in oral/poster presentation competitions at different conferences. (For more details, please see my CV.)

Wei-Tse Hsu
Wei-Tse Hsu
Postdoctoral Research Associate in Drug Design

Computational Biophysicist keen on molecular dynamics, deep learning, and education